This invention relates generally to the use of narcotic antagonists, including naloxone and naltrexone, to counteract the physiological and/or psychological effects of starvation by food and fluid deprivation in animals, including humans. In particular, this invention relates to a method for treating mammals, including humans, with opiate antagonists in order to alleviate weight loss disorders, including anorexia nervosa and bulimia.
Deprivation of food and fluids leading to starvation with accompanying weight loss may be imposed by "circumstances", as, for example, famine, or by others, as, for example, a prisoner of war situation. It may also be self imposed, as in the case of anorexia nervosa and bulimia.
The term "anorexia" refers to a medical symptom indicating a lack or loss of appetite for food (see Dorland's Medical Dictionary, 25th Ed.) which may occur in a variety of medical conditions and diseases. In contrast, the term "anorexia nervosa" denotes a diagnosis of a severe nervous condition characterized by a relentless addiction-like pursuit of thinness to the point of cachexia by voluntarily withholding foods and fluids, and, at times, by excessive exercising, that results from dieting to achieve a socially pleasing slim appearance.
Anorexia nervosa is also associated with physiological changes that include abnormal endocrine and metabolic functions, variations from normal urine concentrations, and a lowering of body temperature, respiratory, and cardiovascular functions. These changes appear to be part of a universal adaptive mechanism of starvation since they are reversible with weight gain and do not differ substantially from those found in other forms of starvation, such as famine or prisoner of war situations.
Bulimia is characterized by excessive intake of food and fluids followed by, or associated with, purgatory maneuvers designed to rid oneself of the ingested food and fluids. Such purgatory self-manipulations include, but may not be restricted to vomiting, use of laxatives and rectal enemas, and depletion of body fluids by diuretic agents. Each of these methods leads to body fluid loss and disturbance of the body's electrolyte balance. Excessive food intake and purging behavior usually results from excessive dieting and can become an addictive compulsive habit, especially in distressed and depressed individuals.
Opiate antagonists are synthetic compounds which may be given to opiate addicts to block the physical and/or psychological effects of opiates. These opiate antagonists include naltrexone and naloxone.
Naloxone is a powerful antagonist of exogenous opiates and naturally occurring opioid peptide hormones which have opiate like effects on the organism. It is a relatively pure opiate antagonist and is administered intravenously. Naltrexone is known to be a powerful antagonist of exogenous opiates and naturally occurring opioid peptide hormones which have opiate like effects on the organism. It may be prepared in accordance with the teachings of U.S. Pat. No. 3,322,950 and Canadian Pat. No. 913,077. Naltrexone is a relatively pure opiate antagonist and is effective when given orally.
Naltrexone has been used in the past to induce anorexia as discussed in U.S. Pat. No. 4,217,353. In that patent, there is discussed certain studies directed principally to the safety and efficacy of naltrexone as an oral narcotic antagonist. In these studies, the patentee notes that there are some isolated and contradictory statements concerning the effect of naltrexone on appetite in man.
One study has suggested the use of naloxone in treating anorexia nervosa. See Moore et al "Naloxone in the Treatment of Anorexia Nervosa: Effect on Weight Gain and Lipolysis", 74 J. Roy. Soc. Med. 129 (1981). This study of the effect of naloxone on anorexics is inconclusive, however, because the naloxone treatment was coupled with hypercaloric feeding (3000-4000 kcal dietary intake) as well as the administration of antidepressant medication (usually amitriptylene). A letter in that same publication suggests that the weight gain described in the Moore et al study might be related to interference with vomiting, both voluntary and involuntary. It also discusses a possible role of opiate antagonists in the therapy of anorexia nervosa. 74 J. Roy. Soc. Med. 631. The "vomiting" explanation was subsequently discussed and dismissed by a co-author of the Moore et al article. 74 J. Roy. Soc. Med. 945.
The search has continued for improved methods of treating weight loss disorders such as anorexia nervosa and bulimia. This invention was made as a result of that search.